Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study

This open-label pilot study (n=5) assessed the effects of six ketamine infusions on participants who had recovered from anorexia nervosa (AN) but had persisting eating disorders thoughts and behaviours. Prior to receiving six ketamine infusions over a 6 month period, participants adopted a therapeutic ketogenic diet. Though the length of the diet varied among participants, the group showed significant improvements on a number of commonly used scales to assess eating disorders.

Abstract

“Purpose: Anorexia nervosa (AN) is a severe psychiatric disorder, and shape and weight concerns are often chronic despite weight normalization. No specific treatments exist for those preoccupations that interfere with recovery and trigger relapse. A case study using a ketogenic diet followed by ketamine infusions led to sustained remission in one patient with chronic AN. Here we conducted an open-label trial to test whether this response could be replicated.

Methods: Five adults weight recovered from AN but with persistent eating disorder thoughts and behaviours adopted a therapeutic ketogenic diet (TKD) aimed at maintaining weight. After sustaining nutritional ketosis, participants received six ketamine infusions and were followed over 6 months.

Results: All participants completed the study protocol without significant adverse effects. Two participants maintained TKD for 8 weeks prior to ketamine infusions due to good behavioural response and remained on TKD. Three participants received TKD for 4 weeks prior to and during ketamine, then tapered off after the final infusion. The group showed significant improvements on the Clinical Impairment Assessment (p = 0.008), Eating Disorder Examination Questionnaire (EDEQ) Global score (p = 0.006), EDEQ-Eating Concerns (p = 0.005), EDEQ-Shape Concerns (p = 0.016), EDEQ-Weight Concerns (p = 0.032), Eating Disorders Recovery Questionnaire (EDRQ) Acceptance of Self and Body (0.027) and EDRQ-Social and Emotional Connection (p = 0.001). Weight remained stable, except for one participant who relapsed 4 months after treatment and off TKD.

Conclusion: This novel treatment appears to be safe and effective for adults with chronic AN-related psychopathology. The results from this open trial support that there are specific neurobiological underpinnings of AN that can be normalized using TKD and ketamine.”

Authors: Lori Calabrese, Barabara Scolnick, Beth Zupec-Kania, Caroline Beckwith, Kayla Costello & Guido K. W. Frank

Summary

A ketogenic diet followed by ketamine infusions led to sustained remission in one patient with chronic shape and weight concerns.

Introduction

Anorexia nervosa is a severe psychiatric disorder that can be treated by a high-fat low-carbohydrate diet and ketamine infusion. The etiology of anorexia remains unclear, but recent research suggests that biological mechanisms that contribute to AN’s pathophysiology may be useful in treating the disorder. Ketamine and ketogenic diet both affect dopamine metabolism and release, which may help normalize altered dopamine function in AN.

A 29-year-old woman with chronic AN experienced complete remission from the disease after adopting a therapeutic ketogenic diet (TKD) similar to that used to treat epilepsy and not designed for weight loss.

In a follow-up trial, individuals with AN who were weight recovered but had significant elevations in AN-typical behaviors were treated with TKD and ketamine and showed substantial improvement.

Participants

Females over the age of 18 with AN for at least 10 years were recruited from the community through targeted advertisements.

Participants had to be screened for eligibility by completing an online screening form, phone interview, and then video interview with the principal investigator. They had to continue current psychiatric medications under the care of their outpatient provider.

Immersion and maintenance of TKD

Each participant was accompanied by an adult support person. They consumed three meals and two snacks daily of ketogenically balanced macronutrients, and the patient who was the index case from our previous case report offered peer support.

Participants measured breath acetone twice daily for 2 weeks, then daily for the remainder of the TKD phase of the study. Weight was recorded daily for 1 week, every other day for 1 week, then weekly until study completion.

Following the immersion program, participants were monitored for safety, TKD adherence and efficacy with daily phone calls, weight and breath acetone monitoring, and weekly optional group meetings.

Ketamine administration

Each participant received six infusions of racemic ketamine over a 17-day period to achieve dissociation. Pulse, blood pressure, respiration, and O2 saturation were monitored throughout the infusion and recovery periods.

Follow‑up

After the sixth ketamine infusion, participants were followed up weekly for 4 weeks, monthly for 3 months, then every 3 months until 6 months with plans to continue follow-up again at months 9 and 12.

Demographic and clinical characteristics

All participants were white females, ages 29 – 45, with major depressive disorder, posttraumatic stress disorder, body dysmorphic disorder, PTSD, sertraline, and generalized anxiety disorder. They received a ketamine dose of 1.3 mg/kg.

Ability to adopt and maintain nutritional ketosis with TKD

All participants maintained nutritional ketosis for at least 4 weeks before receiving ketamine infusions. Two participants continued to maintain nutritional ketosis with breath acetone monitoring for an additional 4 weeks.

Outcome data

Participants provided outcome data, but participant 4 did not provide data on time point 2 (8 weeks) and participant 1 at time point 5 (6-month follow-up). CIA, PHQ, and BMI data were missing for several participants, but last observation carried forward was used to handle missing data.

Discussion

This follow-up study indicates that TKD followed by ketamine infusion treatment normalizes AN-related psychopathology. The underlying mechanisms of TKD and ketamine are unclear, but could involve effects on mitochondria, lipids as signaling agents, adenosine, neuronal stabilization due to less fluctuations in glucose, and changes in the gut microbiome.

While the study sample was small, there were significant changes observed in symptom improvement, and the addition of ketamine provided additional relief. Two individuals remained on the ketogenic diet through the 6-month follow-up.

Strengths and limits

In this study, participants with comorbid MDD and AN received TKD plus ketamine to reduce AN-related psychopathology. The study has limitations, including a small sample size and variable TKD/ketamine dosing.

Conclusions

This study suggests that TKD followed by ketamine infusion treatment can help individuals with AN who have weight normalized but continue to have severe preoccupations with fears of weight gain.